Core Viewpoint - Long COVID is increasingly recognized as a serious condition affecting millions, with no approved treatment options currently available, highlighting the urgent need for effective therapies [1][2][4] Group 1: Long COVID Overview - Long COVID impacts approximately 20 million adults in the U.S. and millions more globally, with 10-30% of COVID-19 patients experiencing lingering symptoms such as fatigue and cognitive impairment [2][5] - The economic impact of long COVID is significant, estimated at $3.7 trillion due to loss in quality of life, earnings, and increased medical costs [5] Group 2: Bezisterim Development - BioVie Inc. has initiated the Phase 2 ADDRESS-LC clinical trial to evaluate bezisterim (NE3107) for treating neurological symptoms associated with long COVID, with topline data expected in the first half of 2026 [1][3] - Bezisterim targets neuroinflammation, which is believed to play a central role in long COVID symptoms, and has shown potential in reducing chronic symptoms in trials for Alzheimer's and Parkinson's diseases [1][3][6] Group 3: Clinical Trial Details - The ADDRESS-LC study is a randomized, placebo-controlled trial involving approximately 200 patients with long COVID experiencing cognitive impairment and fatigue [3][8] - The trial is fully funded by a $13.13 million grant from the U.S. Department of Defense [10] Group 4: Mechanism of Action - Bezisterim is an orally bioavailable, blood-brain barrier-permeable compound that modulates inflammatory pathways implicated in chronic inflammation, potentially improving symptoms in long COVID patients [6][8] - The drug is designed to reduce neuroinflammation and address metabolic dysfunction, which may help restore normal function and improve quality of life for affected individuals [3][4] Group 5: Broader Implications - The persistent presence of SARS-CoV-2 proteins and the resulting inflammatory pathways are linked to prolonged neuroinflammation and symptoms in long COVID patients, indicating a need for targeted interventions [4][8] - BioVie is also conducting trials for bezisterim in Parkinson's and Alzheimer's diseases, demonstrating its broader therapeutic potential [7][9]

Core Insights - Tiziana Life Sciences announced significant results from a PET scan showing a marked reduction in microglia activation in a patient with moderate Alzheimer's disease after three months of treatment with intranasal foralumab, indicating potential efficacy in reducing neuroinflammation associated with the disease [1][5][7] Company Overview - Tiziana Life Sciences is a biotechnology company focused on developing innovative immunomodulation therapies, with its lead candidate being intranasal foralumab, a fully human anti-CD3 monoclonal antibody [1][9] - The company aims to address the urgent need for effective treatments for Alzheimer's disease, particularly in moderate stages, as current approved therapies are lacking [7][9] Treatment Mechanism - Intranasal foralumab works by inducing T regulatory cells (Tregs) that travel to the brain to reduce neuroinflammation, which has been confirmed in both animal models and patients with secondary progressive multiple sclerosis [6][9] - The treatment has shown a favorable safety profile and clinical response in ongoing studies, with all 10 patients in an open-label program experiencing either improvement or stability of their condition within six months [8][9] Research and Development - The findings were presented at the 2025 AD/PD Conference and highlight the need for further studies to explore the effects of foralumab in a broader patient population with moderate Alzheimer's disease [5][7] - Tiziana's innovative nasal delivery approach is expected to enhance the efficacy and safety of immunotherapy compared to traditional intravenous methods [9] Market Context - Alzheimer's disease currently affects over 50 million people worldwide, with projections indicating that this number could triple by 2050, underscoring the critical demand for new treatment options [7][9]

Core Insights - Tiziana Life Sciences announced significant results from a PET scan showing a marked reduction in microglia activation in a patient with moderate Alzheimer's disease after three months of treatment with intranasal foralumab, indicating potential efficacy in reducing neuroinflammation associated with the disease [1][5][7] Company Overview - Tiziana Life Sciences is a biotechnology company focused on developing innovative immunomodulation therapies, with intranasal foralumab as its lead candidate, which is a fully human anti-CD3 monoclonal antibody [1][10] - The company aims to provide alternative routes of immunotherapy, potentially improving efficacy and safety compared to traditional intravenous delivery methods [10] Treatment Efficacy - The PET scan results presented at the 2025 AD/PD Conference indicated a substantial decrease in TSPO signal, suggesting that foralumab may effectively reduce microglial activation, a critical factor in neuroinflammation related to Alzheimer's disease [5][7] - Foralumab has shown promise not only in Alzheimer's but also in other neurodegenerative diseases, including secondary progressive multiple sclerosis, where it has demonstrated stabilization or improvement of symptoms [6][8][10] Market Need - Alzheimer's disease currently affects over 50 million people worldwide, with projections indicating that this number could triple by 2050, highlighting the urgent need for effective treatments, particularly for moderate stages of the disease [7][10]

Summary of Reviva Pharmaceuticals Holdings (RVPH) Conference Call Company Overview - Reviva Pharmaceuticals is a clinical stage pharmaceutical company focused on developing novel therapies for neuropsychiatric diseases, particularly schizophrenia [3][38]. Pipeline and Development - The company has two molecules in development, with biloroxazine being the most advanced, currently in phase three studies for schizophrenia. Over one thousand patients have been treated [3][38]. - Enrollment for a long-term safety study is expected to complete in the next two to four weeks, with full data readout anticipated [3][38]. Core Insights on Schizophrenia - Schizophrenia is characterized by multiple symptom domains: positive, negative, mood, and cognitive symptoms. Most approved antipsychotics primarily address positive symptoms, leaving a significant unmet need for negative symptom treatment and treatment adherence [5][40]. - Neuroinflammation has gained attention as a contributing factor to schizophrenia, with approximately 30% of patients not responding to current treatments [6][40]. Efficacy and Safety Data - Biloroxazine shows a statistically significant efficacy with a ten-point separation from placebo in phase three trials, outperforming other antipsychotics like olanzapine and CAPLYTA [7][8]. - The drug demonstrates robust activity for negative symptoms, a critical area where most antipsychotics show limited efficacy [8][9]. - The discontinuation rate for biloroxazine is reported at 16%, significantly lower than the 30-45% range seen with other antipsychotics [11][13]. - Safety data indicates a clean profile with no significant movement disorders observed, which is a common side effect of other treatments [12][18]. Mechanism of Action - Biloroxazine modulates dopamine and serotonin receptors and has potent activity against neuroinflammatory targets, differentiating it from other antipsychotics [7][16]. - The drug's unique mechanism may enhance efficacy while mitigating side effects, particularly motor side effects [17][19]. Future Development Plans - Beyond schizophrenia, Reviva plans to explore indications for bipolar disorder, major depressive disorder, and ADHD, leveraging the drug's safety profile and efficacy in treating negative symptoms [34][39]. - The ADHD market is estimated at $28 billion, with no new drugs currently in development, presenting a significant opportunity for Reviva [34]. Market Positioning - The company believes biloroxazine will be a differentiated product in the treatment landscape, especially as it addresses both positive and negative symptoms effectively [32][33]. - The drug's development is positioned against both older generic drugs and newer mechanisms, emphasizing the need for effective treatment of negative symptoms [31][32]. Regulatory Pathway - Reviva has engaged with the FDA regarding the phase three study data and plans to conduct a pre-NDA meeting as full data readout approaches [26][27]. Conclusion - Reviva Pharmaceuticals is optimistic about biloroxazine's potential for NDA approval within the next 18 to 24 months, with a strong focus on addressing unmet needs in schizophrenia and expanding into other neuropsychiatric conditions [14][34].

Core Viewpoint - BioVie Inc. is advancing its clinical-stage drug candidate bezisterim (NE3107) for the treatment of early Parkinson's disease, with a Phase 2 clinical trial named SUNRISE-PD set to present findings at the IAPRD 2025 conference in New York City [1][2]. Company Overview - BioVie Inc. (NASDAQ: BIVI) focuses on developing innovative drug therapies for neurological and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and long COVID, as well as advanced liver disease [13]. - The company's lead candidate, bezisterim, is designed to modulate inflammation and enhance insulin sensitivity without immunosuppressive effects, potentially addressing multiple disease indications [8][13]. Clinical Trial Details - The SUNRISE-PD trial is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled study lasting 20 weeks, evaluating bezisterim's safety and efficacy in patients with early Parkinson's disease [3][4]. - Patients can participate either from home or at clinical sites, with remote supervision by neurologists during assessments [4]. Parkinson's Disease Context - Parkinson's disease is characterized by the loss of dopamine-producing neurons, leading to motor and non-motor symptoms that significantly impact patients' quality of life [5]. - Traditional treatments like levodopa have limitations, including long-term complications such as motor fluctuations and dyskinesia [6]. Mechanism of Action - Bezisterim targets chronic inflammation and insulin resistance, which are linked to the progression of Parkinson's disease, by modulating neuroinflammation and metabolic dysfunctions [7][8]. Expected Outcomes - Topline data from the SUNRISE-PD trial is anticipated in late 2025 or early 2026, with previous studies indicating bezisterim's potential to improve motor control and reduce adverse events when combined with levodopa [9][10].

Core Insights - BioVie Inc. has established a Corporate Advisory Board consisting of seven leaders in various fields to enhance its clinical development and business strategy, particularly focusing on neuroinflammatory disorders like Alzheimer's and Parkinson's [1][2][3] Group 1: Corporate Advisory Board - The Corporate Advisory Board aims to support clinical development, inform business strategy, and enhance stakeholder engagement, with members having personal connections to the neuroinflammatory conditions targeted by BioVie [2] - Board members include experts from diverse sectors such as neuroscience, biotechnology, and finance, bringing decades of experience to the company [1][4][5] Group 2: Drug Candidate Bezisterim - Bezisterim (NE3107) is an investigational drug that modulates inflammation and insulin sensitivity, showing potential in treating Alzheimer's, Parkinson's, and long COVID [6][11] - Clinical trials have demonstrated efficacy, with a Phase 3 study for Alzheimer's and a Phase 2 trial for Parkinson's showing promising results in cognitive and motor function improvements [7][8] Group 3: Clinical Development and Research - BioVie is currently enrolling patients for the Phase 2 SUNRISE-PD trial to evaluate bezisterim's effects on Parkinson's disease, with topline data expected in late 2025 or early 2026 [8] - The company has also initiated the ADDRESS-LC study to assess bezisterim's impact on neurological symptoms associated with long COVID, targeting approximately 200 patients [9][10]

Financial Data and Key Metrics Changes - INmune Bio raised $29.9 million from the sale of common stock and warrants in 2024, issuing a total of 4,145,978 shares and warrants for 3,898,852 shares [37][38] - The net loss attributable to common stockholders for the year ended December 31, 2024, was approximately $42.1 million, compared to approximately $30 million for 2023 [40] - Research and development expenses totaled approximately $33.2 million for 2024, up from approximately $20.3 million in 2023 [40] - Cash and cash equivalents at December 31, 2024, were approximately $20.9 million, with an additional $5.4 million raised since year-end [41] Business Line Data and Key Metrics Changes - The ADO2 trial for Alzheimer's disease is expected to announce top-line data in less than 100 days, focusing on neuroinflammation as a primary driver of the disease [8][14] - The INmune platform has pivoted to target solid tumors, with ongoing trials for castrate-resistant metastatic prostate cancer [17][18] - CORDStrom, a new therapeutic platform, is positioned to address systemic disease modification for RDEB, differentiating itself from local wound management therapies [22][24] Market Data and Key Metrics Changes - The ADO2 trial enrolled 208 patients across eight countries, with a focus on those with neuroinflammation driving their Alzheimer's disease [15] - The CaRe PC trial for prostate cancer is progressing, with completion of dosing in the Phase 1 part and ongoing Phase 2 dosing expected to complete by 2025 [18][43] Company Strategy and Development Direction - INmune Bio aims to challenge the amyloid-centric paradigm of Alzheimer's treatment by focusing on neuroinflammation [14][33] - The company is committed to advancing its three therapeutic platforms, with a focus on achieving regulatory milestones and potential commercialization [36][45] - The management emphasizes a precision medicine approach in clinical trials, particularly in the ADO2 trial [10][29] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming results from the ADO2 trial, viewing it as a potential catalyst for a paradigm shift in Alzheimer's treatment [34][35] - The company believes that addressing neuroinflammation could have broader implications for various CNS diseases [35] - Management highlighted the importance of safety in treating elderly patients with Alzheimer's, noting no significant adverse events reported thus far [31] Other Important Information - The company plans to file a BLA for CORDStrom in the first quarter of 2026, which would mark its first market therapeutic [44][112] - Management is focused on ensuring the quality of regulatory submissions to facilitate successful approvals [113] Q&A Session Summary Question: Is the 12-month open label trial for RDEB required for filing? - Management indicated that they believe the current data is adequate for a BLA submission, but the FDA will ultimately decide [50][51] Question: Will EMACC and CDR results be released at the same time? - Management confirmed that both EMACC and CDR results will be available at the time of data release [56][60] Question: Are there any dropouts in the EXPAREL Phase 2 trial? - Management reported that dropouts are within expected ranges, primarily due to typical issues associated with elderly patients [86] Question: How does the company plan to commercialize CORDStrom? - Management aims to move towards commercialization independently but may seek a partner closer to the launch [93] Question: Will the BLA for CORDStrom be filed in the UK and US? - Management confirmed that they expect to have all necessary data ready for filing in both regions by early 2026 [101][102]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for the year ended December 31, 2024, was approximately $42.1 million, compared to approximately $30 million for 2023, indicating a significant increase in losses [41] - Research and development expenses totaled approximately $33.2 million for the year ended December 31, 2024, compared with approximately $20.3 million for 2023, reflecting a substantial increase in investment in R&D [41] - General and administrative expenses were approximately $9.5 million for the year ended December 31, 2024, compared with approximately $9.6 million for 2023, showing a slight decrease [41] - As of December 31, 2024, the company had cash and cash equivalents of approximately $20.9 million, with an additional $5.4 million raised since year-end through the use of the ATM [42] Business Line Data and Key Metrics Changes - The ADO2 trial for Alzheimer's disease enrolled 208 patients across eight countries, with nearly 800 patients screened, indicating a rigorous patient selection process [15][16] - The CARE-PC trial using IncMUNE for treating metastatic prostate cancer has made steady progress, with completion of dosing in the Phase 1 dose escalation part and ongoing dosing in the Phase 2 part [18] Market Data and Key Metrics Changes - The company has pivoted to solid tumors with the INCMUNE platform, believing that future opportunities are greater in this area compared to hematologic diseases [17] Company Strategy and Development Direction - The company aims to challenge the traditional amyloid-centric paradigm of Alzheimer's disease treatment by focusing on neuroinflammation as a primary driver [14][35] - The addition of Cordstrom has introduced a third therapeutic platform, which is expected to accelerate the timeline to becoming a commercial entity [37] - The company plans to file a Biologics License Application (BLA) for Cordstrom in the first quarter of next year, marking a significant milestone towards revenue generation [45] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming results from the ADO2 trial, viewing it as a potential catalyst for a paradigm shift in Alzheimer's treatment [35][36] - The company is focused on achieving primary clinical objectives while remaining cost-prudent, with expectations of sufficient cash to fund operations through Q3 2025 [42][43] Other Important Information - The company has received orphan drug status and rare pediatric disease designation for Cordstrom, differentiating it from other therapies by providing a systemic disease-modifying approach [22] Q&A Session Summary Question: Is the 12-month open-label trial required for filing? - Management indicated that they have access to all clinical data from the current trial and believe it will be adequate for a BLA submission [51] Question: Will the EMAC and CDR results be staggered? - Both EMAC and CDR results will be released simultaneously when the data becomes public [56][57] Question: Are there any dropouts in the Phase II trial? - Dropouts are less than expected, primarily due to typical elderly-related issues rather than drug efficacy or safety concerns [76] Question: How does the company plan to commercialize Cordstrom? - The company aims to move forward independently but may seek a partner for distribution and marketing as they approach commercialization [82][83] Question: Will the BLA for Cordstrom be filed in the UK and US? - The company expects to have all necessary data ready for filing in the first quarter of 2025, with ongoing preparations for both markets [90][91]

Summary of InMed Pharmaceuticals (INM) Update / Briefing Industry Overview - The discussion centers around the Alzheimer's disease research and development landscape, highlighting the recent advancements in disease-modifying therapies and the challenges faced in clinical trials and drug development [6][7][15]. Key Points and Arguments Advances in Alzheimer's Research - There has been a significant increase in understanding Alzheimer's disease over the past decade, with the first disease-modifying therapies launched in the U.S., Japan, and China [6][7]. - The removal of amyloid from the brains of patients has been achieved, impacting tau levels and disease progression, although the average clinical impact remains limited [15][16][18]. Challenges with Mouse Models - Current mouse models primarily focus on amyloidosis and tauopathy, which do not fully replicate the complexity of Alzheimer's disease [8][9][10]. - The efficacy of treatments is often tested in younger mice, which may not accurately reflect the disease's progression in older adults [10][11]. - Advanced-stage models are necessary to better understand the safety and efficacy of treatments [11][13]. Importance of Biomarkers - The selection of patients for clinical trials has evolved from clinical criteria to biomarker-based criteria, improving the ability to demonstrate clinical efficacy [21][22]. - There is a need for better biomarkers for neuroinflammation, which is still in early development compared to amyloid biomarkers [47][48]. Neuroinflammation as a Target - Chronic neuroinflammation is recognized as a significant factor in Alzheimer's disease, with potential drug targets being explored [32][33][36]. - InMed's compound, INM901, shows promise in modulating neuroinflammation and promoting neurogenesis, with positive results in animal studies [30][51][52]. Diversity in Clinical Trials - Current clinical trials have been criticized for lacking racial and ethnic diversity, which may affect the understanding of drug efficacy across different populations [18][20][60]. Future Directions - The panelists express optimism about the future of Alzheimer's research, emphasizing the need for combination therapies and the potential for repurposing existing drugs [41][65]. - The goal is to transform Alzheimer's from a terminal disease to a chronic condition, improving the quality of life for patients [88][89]. Other Important Content - The discussion highlights the iterative learning process in selecting patients for trials based on biomarkers rather than solely on clinical diagnosis [21][22]. - The role of inflammation in Alzheimer's is complex, with both beneficial and harmful effects depending on the disease stage [40][76]. - The importance of accurate diagnosis and the distinction between Alzheimer's disease and dementia is emphasized [103]. This summary encapsulates the key discussions and insights from the InMed Pharmaceuticals update, focusing on the current state and future directions of Alzheimer's disease research and treatment.